Eastern, Western and Venezuelan equine encephalomyelitis result from infection by the respectively named viruses in the genus Alphavirus (family Togaviridae). In the human literature, the disease is usually called Eastern, Western or Venezuelan equine encephalitis.

Eastern Equine Encephalomyelitis Virus
There are two variants of the Eastern equine encephalomyelitis (EEE) virus. The virus found in North America is more pathogenic than the variant that occurs in South and Central America. The Eastern equine encephalitis virus can cause disease in humans, horses and some species of birds.

Western Equine Encephalomyelitis Viruses
The Western equine encephalomyelitis (WEE) virus group includes the Western equine encephalitis (WEE), Sindbis, Ft. Morgan, Aura and Y 61-33 viruses. The Western equine encephalitis virus can cause disease in humans, horses and some species of birds. A related virus, the Highlands J virus, is sometimes isolated in the eastern United States. The Highlands J virus can cause disease in turkeys. It has also been linked to a single case of encephalitis in a horse.

Venezuelan Equine Encephalomyelitis Viruses
The Venezuelan equine encephalomyelitis (VEE) complex contains at least 8 viral subtypes; these viruses are divided into epizootic and enzootic groups. The epizootic subtypes are responsible for most epidemics. They are highly pathogenic for horses and also cause illness in humans. Enzootic (sylvatic) subtypes are generally found in limited geographic areas, where they occur in natural cycles between rodents and mosquitoes. The enzootic subtypes can cause human disease. They are usually nonpathogenic for horses; however, in 1993 an enzootic variant was responsible for an outbreak of VEE among horses in Mexico.

Geographic Distribution

The Western, Eastern and Venezuelan encephalomyelitis viruses are found in North, Central and South America. The WEE viruses occur in western Canada, Mexico, parts of South America, and west of the Mississippi in the United States. The EEE virus is found in eastern Canada, all states east of the Mississippi, Arkansas, Minnesota, South Dakota and Texas. It also occurs in the Caribbean and regions of Central and South America, particularly along the Gulf coast. VEE viruses are endemic in South and Central America and Trinidad. Enzootic subtypes of VEE are also found in Florida, the Rocky Mountains and northern plains of the United States. Most epidemics of VEE occur in northern and western South America, but some may spread into adjacent countries, including the United States.

Transmission

Eastern and Western Equine Encephalomyelitis
The Eastern and Western encephalomyelitis viruses are transmitted mainly by mosquitoes. Normally, these two viruses cycle between birds and mosquitoes. Humans and horses are incidental, dead end hosts.

The EEE virus can be isolated from 27 species of mosquitoes in the United States. Culiseta melanura, a mosquito that primarily feeds on birds, is the most important vector in the enzootic cycle. During some years, the virus is spread to mammalian hosts by bridge vectors (mosquitoes that feed on both birds and mammals) such as Coquilletidia perturbans, Aedes canadensis, Aedes sollicitans, Aedes vexans and Culex nigripalpus. WEE cycles between passerine birds and culicine mosquitoes. Culex tarsalis appears to be the most important vector; other significant vectors include Aedes melanimon, Aedes dorsalis and Aedes campestris. The EEE and WEE viruses may be transmitted vertically in mosquitoes.

In birds, EEE and WEE are occasionally spread by non-arthropod-borne routes. During outbreaks of disease in game birds, infections are introduced by mosquitoes but spread in the flock mainly by feather picking and cannibalism. EEE and WEE viruses do not survive outside the host.

Venezuelan Equine Encephalomyelitis
The Venezuelan equine encephalomyelitis viruses are also spread mainly by mosquitoes. The enzootic subtypes of VEE cycle between rodents and mosquitoes, mainly Culex species. Birds may also be involved in some cycles. Humans and horses are incidental hosts.

The natural host for the epizootic subtypes, between epidemics, is unknown. Horses infected with the epizootic subtypes can infect mosquitoes and are the main amplifiers for VEE during epidemics. Other mammals, including cattle, pigs and dogs, can be infected but do not usually become ill or spread the virus. Many different species of mosquitoes and other hematogenous insects can transmit epizootic VEE. Efficient vectors include arthropods in the genera Aedes, Anopheles, Culex, Deinocerites, Mansonia, Haemogogus, Sabethes and Psorophora.

In some cases, humans have also developed VEE after being exposed to debris from the cages of infected laboratory rodents. Person-to-person transmission has not been reported; however, the VEE virus can be found in pharyngeal secretions in humans and is stable when aerosolized. The virus can also occur in dried blood and exudates.

Disinfection

EEE and WEE viruses do not persist in the environment but the VEE virus may be found in dried blood and exudates. VEE, EEE and WEE are susceptible to many disinfectants including 1% sodium hypochlorite, 70% ethanol, 2% glutaraldehyde and formaldehyde. They can also be destroyed by moist or dry heat, as well as drying.

Infections in Humans

Incubation Period

In humans, the incubation period is usually 1 to 6 days for VEE and 4 to 15 days for WEE and EEE.

Clinical Signs

Eastern and Western Equine Encephalitis
Eastern equine encephalitis usually begins abruptly, with fever, myalgia and headache and sometimes nausea and vomiting. This prodrome is often followed by neurologic signs; the symptoms may include confusion, focal neurologic deficits, somnolence, neck stiffness, stupor, disorientation, coma, tremors, seizures and paralysis. Abdominal pain, diarrhea and a sore throat can also occur. The mortality rate for EEE is high.

Western equine encephalitis resembles EEE but is usually asymptomatic or mild in adults, with nonspecific signs of illness and few deaths. The symptoms usually appear abruptly and may include fever, headache, nausea, vomiting, anorexia and malaise. Many adults do not develop other symptoms. In more severe cases, neurologic symptoms, similar to those seen in EEE, can develop. WEE can be severe in children, particularly infants under a year of age.

Venezuelan Equine Encephalitis
In humans, VEE is usually an acute, often mild, systemic illness. The clinical signs may include fever, generalized malaise, severe headache, photophobia and myalgia, particularly in the legs and lumbosacral region. These symptoms usually last for 24 to 72 hours and may be followed by a cough, sore throat, nausea, vomiting and diarrhea. The disease usually lasts 1 to 2 weeks. In pregnant women, VEE can affect the fetus; fetal encephalitis, placental damage, abortion or severe congenital neurologic anomalies may be seen.

Encephalitis usually develops in 4% of children and less than 1% of adults. In mild cases, the symptoms may include lethargy, somnolence, or mild confusion. Severe infections are characterized by seizures, ataxia, paralysis or coma. An increased incidence of encephalitis would be expected after a biological attack with aerosolized viruses.

Communicability

WEE and EEE viruses are not found in the blood or cerebrospinal fluid after the symptoms appear, and only low titers develop during the viremic phase. These viruses do not seem to be spread directly from person to person. Humans do not transmit EEE or WEE viruses to mosquitoes.

Person-to-person transmission is theoretically possible for VEE, but has not been reported in natural cases. Humans with VEE can infect mosquitoes for approximately 72 hours.

Diagnostic Tests

Eastern, Western and Venezuelan equine encephalitis can be diagnosed by virus isolation, serology or other tests. In humans, VEE virus can be isolated from blood, cerebrospinal fluid or throat swabs. Serology is also useful; a rise in titer or the presence of specific IgM is diagnostic. A variety of serologic tests may be available, including virus neutralization, ELISA, hemagglutination inhibition and complement fixation. Indirect immunofluorescence assays have been developed for VEE. Polymerase chain reaction (PCR) or immunohistochemistry may be available at some laboratories.

During the febrile stage of the illness, antigen-capture ELISAs can often detect VEE antigens in the blood. This test is generally not useful during the encephalitic stage. PCR assays may also be available.

Treatment and Vaccination

Treatment consists of supportive care. Investigational VEE, EEE and WEE vaccines may be available for humans at high risk of infection. The VEE vaccine may not be effective for all of the VEE complex viruses.

Morbidity and Mortality

Eastern Equine Encephalitis
In the United States, approximately 12 to 17 cases of EEE are reported to the Centers for Disease Control and Prevention (CDC) each year. The infection rate is approximately 33% and the morbidity rate 90%. Most cases are seen in people over 55 and children younger than 15. Eastern equine encephalitis is often severe in humans. Estimates of the case fatality rate vary from 33 to 70% and permanent neurologic deficits can occur in survivors.

Western Equine Encephalitis
The annual incidence of WEE is highly variable; during an epidemic in 1941, over 3000 human cases occurred in the United States and Canada. The case-infection ratio is approximately 1:1000 in adults, 1:58 in children from 1 to 4 years old and 1:1 in infants up to a year of age. The overall mortality rate is 3 to 4%. Most infections in adults are asymptomatic or mild, without neurologic disease. Infections in children, particularly infants under one year old, can be severe. Approximately 5 to 30% of young patients have permanent neurologic damage.

Venezuelan Equine Encephalomyelitis
In natural epidemics of VEE, human cases are usually preceded by an epidemic in horses. After an attack by a biological weapon, cases would be expected simultaneously in both species or first in humans. Caution should be used in interpreting such patterns of infection, as VEE may be missed in wild or free-ranging equines.

Humans are highly susceptible to VEE; approximately 90 to 100% of exposed individuals become infected and nearly 100% of these infections are symptomatic. However, most infections are mild. Less than 1% of adults develop encephalitis and approximately 10% of these cases are fatal. The overall case fatality is less than 1%. Very young or elderly patients are more likely to develop severe infections. Encephalitis occurs in approximately 4% of children less than 15 years old; the case fatality rate in children with neurologic disease is 35%. A higher incidence of neurologic disease could be seen in adults as well as children after a biological attack with aerosolized virus; mortality rates would be expected to be correspondingly higher.

Infections in Animals

Species Affected

The equine encephalomyelitis viruses usually cause illness only in equine species and humans. These viruses can also infect a variety of other animals, often asymptomatically.

Eastern and Western Equine Encephalomyelitis
Eastern equine encephalitis virus infects horses, pigs, birds, bats, reptiles, amphibians, forest-dwelling marsupials and rodents. WEE virus can infect birds, horses and a variety of mammals. Most WEE and EEE infections in birds are asymptomatic; however, disease can be seen in chukar partridges, pheasants, psittacine birds, ratites and whooping cranes.

Venezuelan Equine Encephalomyelitis
Rodents seem to be the natural hosts for the enzootic subtypes of VEE but, in some cases, birds may also be involved. VEE virus can cause serious disease in horses, mules, burros and donkeys. Cattle, pigs and dogs can be infected asymptomatically. VEE can also infect a wide variety of laboratory animals.

Incubation Period
The incubation period for WEE or EEE is 5 to 14 days. The clinical signs of VEE are usually seen 1 to 5 days after infection.

Clinical SignsEastern and Western Equine Encephalomyelitis in Horses
Eastern and Western equine encephalomyelitis are very similar in horses. The initial clinical signs are usually fever, anorexia and depression. In severe cases, this prodromal stage is followed by neurologic signs; the symptoms may include involuntary muscle movements, impaired vision, aimless wandering, head pressing, circling, an inability to swallow, ataxia, paresis, paralysis and convulsions. Periods of excitement or intense pruritus can also be seen. Laterally recumbent animals may develop a characteristic “paddling” motion. Both EEE and WEE can also cause asymptomatic infections or mild disease without neurologic signs. Occasional cases of encephalitis have been seen in pigs.

Venezuelan Equine Encephalomyelitis in Horses
The enzootic subtypes usually infect horses subclinically. The epizootic subtypes can cause asymptomatic infections or two clinical syndromes. One syndrome resembles EEE and WEE; in this form, a febrile prodrome is followed by neurologic signs and sometimes diarrhea and colic. Death can occur within hours after the onset of neurologic signs or after protracted disease. Animals that recover may have permanent neurologic signs. The second form of VEE is a generalized acute febrile disease without neurologic signs. The symptoms may include fever, weakness, depression, anorexia, colic and diarrhea.

Western and Eastern Equine Encephalitis Viruses in Birds
Western and Eastern equine encephalomyelitis virus infections are asymptomatic in most species of birds, but fatal infections can occur in some species. Most reported outbreaks have been caused by EEE. Chukar infected with the EEE virus are usually dull and listless, with ruffled feathers. The birds are typically found sitting on their hocks with the beak on the ground. In pheasants, the symptoms may include incoordination, weakness and progressive paralysis. In the late stages of the disease, the birds cannot stand but can still move their wings. Whooping cranes may develop lethargy, ataxia and paresis of the legs and neck. The EEE virus has also been isolated from psittacine birds with viral serositis.

Both EEE and WEE viruses can cause fatal hemorrhagic enteritis in ratites; the characteristic clinical signs include depression, hemorrhagic diarrhea, and vomiting of bloodstained material. Highlands J and EEE infections can also cause depression, somnolence, decreased egg production and increased mortality in turkeys.

Communicability

Birds can amplify the Western and Eastern equine encephalomyelitis viruses and are infectious for mosquitoes. Horses are dead-end hosts for these viruses. Direct transmission has been seen only between birds.

Both horses and birds infected with the VEE virus are infectious for mosquitoes. In horses, the virus can be found in bodily fluids. Some authorities suggest that transmission may be possible by direct contact or aerosols but natural transmission between horses or from horses to humans has not been seen. Humans can be infected by laboratory rodents.

Diagnostic Tests

Eastern and Western Equine Encephalomyelitis
In horses, Eastern and Western equine encephalomyelitis can be diagnosed by serology. Tests include plaque reduction neutralization (PRN), hemagglutination inhibition, antibody-capture enzyme linked immunosorbent assay (ELISA) and complement fixation. Cross-reactions may occur between EEE and WEE antibodies in the complement fixation and hemagglutination inhibition tests.

Clinical infections in birds are usually diagnosed by virus isolation. In horses, virus isolation is useful in cases of EEE; it is rarely successful in WEE. The EEE virus can usually be recovered from the brain of infected horses; other tissues such as the liver or spleen may also be positive. EEE and WEE viruses can be isolated in newborn mice, embryonating chicken eggs, newly hatched chicks or cell cultures including primary chicken or duck embryo fibroblasts, African green monkey kidney (Vero), rabbit kidney (RK-13), and baby hamster kidney (BHK-21) cells. Virus identity can be confirmed by complement fixation, immunofluorescence or plaque reduction neutralization (PRN) tests. EEE viruses can also be detected in the brain with immunohistochemistry or an antigen-capture ELISA.

Venezuelan Equine Encephalomyelitis
VEE can be diagnosed by virus isolation or serology. VEE virus can often be recovered from the blood during the febrile stage and is sometimes isolated from the brain of animals with encephalitis. Virus is also found occasionally in the pancreas or other tissues. Animals with neurologic signs are not usually viremic. VEE virus can be isolated in guinea pigs, hamsters, mice, embryonated chicken eggs or cell lines including Vero, RK-13, BHK-21 and duck or chicken embryo fibroblasts. The virus can be identified by complement fixation, hemagglutination inhibition, plaque reduction neutralization (PRN) or immunofluorescence assays. Subtypes can be characterized by immunofluorescence, differential PRN tests or nucleic acid sequencing.

VEE can also be diagnosed by serology. Serologic tests include the PRN test, complement fixation, hemagglutination inhibition and ELISAs. Cross-reactions can occur between VEE, EEE and WEE viruses in the hemagglutination inhibition test. Animals may have pre-existing antibodies to enzootic variants of VEE.

Treatment and Vaccination

Treatment consists of supportive care. Equine vaccines are available for EEE, WEE and VEE. EEE vaccines are also available for susceptible birds, but do not always prevent disease.

Morbidity and Mortality

Eastern and Western Equine Encephalomyelitis
WEE often occurs as sporadic cases of encephalitis in horses, scattered over a wide area. Clinical cases of EEE are usually more clustered. EEE is often fatal in horses; the mortality rate is 50 to 90%. WEE is more likely to be asymptomatic or mild, with mortality rates of approximately 20 to 30%. Significant morbidity and mortality can also occur in poultry, game birds and ratites. In pheasants and other susceptible species of birds, both the morbidity and mortality rates may be up to 90%. The morbidity and mortality rates for emus with hemorrhagic enteritis can be greater than 85%.

Venezuelan Equine Encephalomyelitis
Most enzootic VEE subtypes do not result in serious disease or deaths in horses. Epizootic subtypes can cause significant morbidity and mortality; the morbidity rate can be as high as 90% and the mortality rate varies from 30 to 90%.

Post-Mortem Lesions

The gross lesions are usually nonspecific. In horses with VEE, the lesions in the central nervous system vary from no lesions to extensive necrosis with hemorrhages. Necrotic foci are sometimes seen in the pancreas, liver and heart of horses with VEE. Congestion of the brain and meninges is found in some cases of EEE and WEE. Antemortem trauma can result in ecchymotic hemorrhages.

Microscopic analysis of the brain tissue is often diagnostic. The typical lesion is severe inflammation of the gray matter; neuronal degeneration, infiltration by inflammatory cells, gliosis, perivascular cuffing and hemorrhages may be seen. WEE, EEE and VEE can sometimes be differentiated by the location and pattern of the lesions in the brain.